Pneumonectomy (PNX) provides a powerful experimental tool for studying mechanisms of compensatory response to quantifiable losses of alveolar capillary surface area, increased power requirements of ventilation, asymmetrical distortions of the heart and respiratory pumps, and increased pulmonary vascular resistance from a known loss of vascular bed. Mechanisms include recruitment of capillary reserves, lung growth, hypertrophy of heart and respiratory muscles. Relative importance and limits of these mechanisms are unclear. In adult dogs the nature and extent of compensation after pneumonectomy is dependent on the extent of resection; relative compensation is more vigorous after 58% resection than after 42%. Alveolar lung growth is stimulated after 58% resection but not after 42%. Compensatory alveolar growth is not accompanied by airway growth; airway resistance and ventilatory power requirements remain significantly elevated after left or right pneumonectomy. Anatomical distortion of the diaphragm and intercostal muscles may further contribute to derangement of respiratory muscle mechanics. Our objectives are to define the limits and mechanisms of functional impairment and compensation in dogs after extensive lung resection. We ask the following questions: 1) Do ventilatory limitations significantly contribute to the reduced maximal O2 uptake after pneumonectomy? 2) What are the limits of structural and functional compensation? Our hypothesis is that compensatory alveolar lung growth will be even more vigorous after 68% resection but ultimate functional capacity will be less than after either 42 or 58% resection because of greater ventilatory impairment owing to more extensive loss of airway cross-sectional area, the absence of compensatory airway growth, and/or anatomical distortion of the respiratory pump. To address Question 1 maximal O2 uptake will be measured with no external load, with external loads that increase work of breathing 2 to 3 fold and with the system unloaded by breathing a He-O2 mixture. Static and dynamic measurements of lung and thoracic compliance and resistance will be measured to provide estimates of total work of breathing. Respiratory muscle blood flow requirements during exercise will be determined by the fluorescent microsphere technique simultaneously with measurements of ventilation and ventilatory power. To address Question 2, two-stage lung resections will be performed, removing 68% of lung either by unbalanced resection (right PNX+left upper lobectomy) resulting in mediastinal shift and anatomical distortion of the diaphragm and intercostal muscles, or by balanced resection (bilobectomy on each side) leaving equal lung volumes in each hemithorax without mediastinal shift and asymmetrical distortion of respiratory muscles. Comparison of these groups examines the effects of anatomical respiratory muscle distortion at a fixed level of expansion of the remaining lung. Compensatory mechanisms will be studied functionally in the awake dog at rest and exercise and structurally after euthanasia by morphometry of both the lung and respiratory muscles.